Many pharmaceuticals are required to be administered to patients by injection. A notable example is insulin, which cannot be administered orally to be effective in lowering the elevated blood sugar levels, which are too high in diabetics (i.e., &gt;126 mg/dL). Other pharmaceuticals may be administered orally, but in some cases, there is inefficient absorption into the bloodstream to permit the pharmaceuticals to achieve their intended therapy. Also, with regard to oral administration, many orally administered pharmaceuticals undergo a high degree of destruction by the hepato-gastrointestinal first-pass metabolism. Often the metabolites of the first-pass metabolism cause unwanted biological activity or toxicity. In oral administration, there are variables which cause undesirable variations in the extent of gastrointestinal absorption from subject to subject, especially in the case of some pharmaceuticals; and there are also associated problems of uneven blood levels resulting from an initial large absorption with attendant undesirable side effects or toxicities, and subsequent blood levels which are less than therapeutically optimal.
Recently there has been an increasing interest in transdermal delivery. However, transdermal absorption of a number of pharmaceuticals, particularly the macromolecular drugs such as insulin and cationic drugs like propranolol HCl, has not been satisfactorily developed for adequate therapy, since they have not been absorbed transdermally to any significant degree.
The hazard and discomfort of administration of pharmaceuticals by injection, especially if therapy is required on a frequent basis, such as the subcutaneous injection of insulin for diabetes therapy, which is required daily, are universally known. There has long been a desire to avoid the necessity of therapy by injection.
Investigations have been carried out to explore the possibility of delivering certain therapeutic agents topically by use of a direct current (DC) iontophoresis. For example, it has been found that fluoride ions can be assimilated into the structure of a tooth with the aid of DC iontophoresis. Also, localized "sweating" has been caused by delivering to the skin a sweat-inducing compound, such as pilocarpine, using a direct current. The induced sweat is then assayed using an electrode to determine its chloride ion concentration for diagnosis purposes. A low chloride content in the sweat indicates that a patient may be suffering from cystic fibrosis. Application of a DC iontophoresis can be uncomfortable particularly when the level of applied current is at a high level, in the case of certain pharmaceuticals, in order to achieve a systemic therapeutic level.
It is highly desired to provide improved iontotherapeutic devices and processes and unit dose forms for use therein and to provide further thereby therapeutic levels of systemically-effective pharmaceuticals efficiently with a physiologically-acceptable low electric current.